Aislinn Antrim, Associate Editor

New data from the Real-World Evidence of FreeStyle Libre (RELIEF) study have found that the FreeStyle Libre system can help significantly reduce acute diabetes-related events, such as severe hypoglycemia and diabetic ketoacidosis.

FreeStyle Libre is a continuous glucose monitoring system (CGM) and is the most widely used CGM system worldwide, according to an Abbott press release. It is used by more than 4 million patients living across more than 60 countries.

Once-daily insulin therapy is often used when oral medications are no longer sufficient to regulate glucose levels. However, research has shown that patients with type 2 diabetes who start with basal insulin therapy are 3 times more likely to experience severe hypoglycemia.

The retrospective RELIEF study found that 5933 patients with type 2 diabetes who were following a basal insulin-only regimen and using the FreeStyle Libre System had 67% fewer acute diabetes event-related hospitalizations 1 year after initiating treatment with the system. The data also show a 75% reduction in hospitalizations for diabetic ketoacidosis as well as a 44% reduction in admissions for severe hypoglycemia.

Finally, the study also showed sustained reductions in hospitalizations over a 2-year period of FreeStyle Libre system use, regardless of whether the patients were under the care of a diabetes specialist or a general health care practitioner.

“The results of the RELIEF study highlight the value of [the] FreeStyle Libre system in reducing serious diabetes-related events and hospitalizations among patients with type 2 diabetes on basal-only therapy,” said researcher Jean-Pierre Riveline, MD, in the press release. “The reductions are similar to the results seen among the larger cohort of people with type 2 diabetes who were receiving multiple daily injections, suggesting that FreeStyle Libre technology therapy should be proposed as part of individualized care for patients with type 2 diabetes on basal-only insulin, not just people on intensive insulin therapy.”

Fear of hypoglycemia affects many individuals with type 2 diabetes as well as physicians. This fear can sometimes be a barrier to intensifying treatment and impacts patients’ willingness to follow basal insulin therapy as prescribed by their physician.

Findings from the RELIEF study suggest that reducing the incidence of hypoglycemia and diabetic ketoacidosis could improve adherence and help patients with diabetes achieve their glycemic targets. This could be especially impactful for older adults, in whom hypoglycemia is associated with a significantly increased risk of falls, fractures, dementia, and death, according to the study.

“Moving from oral medications to insulin therapy can have a big impact on people with type 2 diabetes, both mentally and physically,” said Alexander Seibold, MD, PhD, senior medical director in Abbott’s diabetes care division, in the press release. “Although the risk is often necessary to manage glucose levels, it can be stressful to inject insulin, which comes with associated risks.”

The results add to a growing body of evidence showing the FreeStyle Libre system’s efficacy in reducing hospitalizations for patients with both type 1 and type 2 diabetes on multiple daily injections of insulin. The system includes a sensor that is applied to the back of the upper arm for up to 14 days, paired with a reader or a smartphone app.

New data show that Abbott’s FreeStyle Libre system reduces diabetes-related hospitalizations for people with type 2 diabetes on once-daily insulin therapy. News release. Abbott; September 20, 2022. Accessed September 22, 2022. 

https://abbott.mediaroom.com/2022-09-20-New-Data-Shows-That-Abbotts-FreeStyle-Libre-System-Reduces-Diabetes-related-Hospitalizations-for-People-with-Type-2-Diabetes-on-Once-daily-Insulin-Therapy

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The study also showed sustained reductions in hospitalizations over a 2-year period of FreeStyle Libre system use.

FreeStyle Libre System Reduces Diabetes-Related Hospitalizations for Patients with Type 2 Diabetes

A new program from the Office of Research on Women’s Health (ORWH) in the National Institutes of Health (NIH) is aiming to improve sex- and gender-specific training in science, medicine, and other health care professions by supporting curricula and courses that address the intentional integration of sex and gender considerations into NIH research. Specifically, as breakthroughs in women’s health research continue to occur at every stage of the biomedical research continuum, the paradigm shift from inclusion of women to the intentional integration of sex- and gender-related differences and information requires the development of new skills and innovative methodologies.

Galvanizing Health Equity Through Novel and Diverse Educational Resources (GENDER)

R25, will fund courses and curricula for health care professionals at any career stage to help address issues related to how health is influenced by sex as a biological variable and/or gender as an identity, social, cultural, or structural variable. NIH officials will also host a technical assistance webinar on Wednesday, September 21, for all health care professionals who want to learn more; funded projects will result in the development of curricula, courses, and methods that can be utilized across disciplines and will be made available through the 

Specifically, Elizabeth Barr, PhD, an ORWH social and behavioral scientist administrator, explained further in an interview with 

 that ORWH welcomes applications from pharmacy professionals, as well as other biomedical communities, as pharmacists are critical members of patient health care teams with direct impact on managing adverse effects (AEs), dosage, and polypharmacy—all of which can impact women more than men due to the limited nature of data  on these subjects in relation to sex and gender-related differences.

“Despite concerted efforts, sex and gender remain underexplored in curricula within biomedical educational programs, including pharmacy programs,” Barr said. “As each health profession has its own discipline-specific language and accreditation standards, pharmacy professionals are ideally positioned to develop curricula to fill the gap within their field; we are hopeful that pharmacy professionals will consider submitting applications for the GENDER R25.”

With the understanding of the clear impacts sex and gender have on health, using clear terminology for sex and gender is essential to facilitate a more accurate study of human health and the delivery of health care by professionals in the field. The classification of sex—which is a multidimensional construct based on clusters of anatomical and physiological traits—can include external genitalia, secondary sex characteristics, gonads, chromosomes, and hormones. Gender, however, is often misunderstood as being an extension of or synonym for sex; instead, gender is a social and cultural variable that includes a variety of domains, including gender identity and expression, gender roles and norms, gender relations, structural sexism, power, and equity.

“Understanding the influence of gender on health...can facilitate the delivery of equitable care by all biomedical professionals,” Barr said. “Pharmacy professionals could all benefit from an enriched understanding of the domains of sex and gender [in their practices].”

By understanding the differences in terminology and the impact of both sex and gender on patient health, pharmacy professionals can better provide more effective individualized, patient-centered services. For example, at the individual level, health care professionals themselves can impact patient health care  outcomes based on the results of 1-on-1 communication with patients regarding the patients experience of symptoms.

Moreover, gender can impact patient health on a relational and structural level as well. On the relational level, gender may have an impact on whether or not a patient may be experiencing intimate partner violence in their home setting, while structural impacts of gender can include varying levels of access to health care based on geographic location for certain female-specific conditions.

Federal law and NIH policy require clinical research funded by the NIH to include women, minorities, and individuals across the lifespan. Importantly, however, this does not only include enrolling women in studies, but must also require considering research design. Studies must be designed to detect the influence of sex on efficacy and safety. If women are included but sex-specific results are not collected and reported, women and health care professionals lack crucial knowledge that can influence patient health.

Further, sex differences can also have impacts on treatment outcomes, such as through varying levels of absorption, metabolism, and excretion of drugs. For example, women typically have different amounts of adipose tissue, different hormonal environments, and may have different kidney and liver functions compared with men, all of which can influence dosages and AEs. Despite these known impacts, women are often underrepresented in clinical trials, leading to results that may not be disaggregated by sex with potential drug distribution differences remaining unidentified.

Gender can also impact whether and how patients report AEs, as well as how those effects are perceived by health care professionals. Women have frequently reported that they experienced the dismissal of their reported symptoms in health care settings, with this experience confirmed in research published in professional journals. This dismissal of symptom experience can result in delayed dose adjustments, accumulative AEs, and even discontinuation of effective therapies.

Sex and gender issues also remain underexplored in biomedical education programs, including those in pharmacy schools. Due to their work with multiple specialists and health experts on patient care teams, pharmacists are perfectly positioned to have a critical role in impacting discussions of sex and gender differences and the use of appropriate terminology for patients by filling in gaps during communication with these professionals. GENDER R25 can help support pharmacists in these efforts by improving their education on these issues in pharmacy programs, which can also be utilized across other disciplines.

For pharmacists interested in learning more, the technical assistance webinar on Wednesday, September 21 will provide potential applicants a chance to learn about the scope, purpose, and requirements for the GENDER R25 program. Staff members at ORWH, participating NIH institutes and centers, and members from the NIH Center for Scientific Review will also be participating in the discussion to provide further details about the program and answer applicants’ questions. For those interested in applying for funding, non-AIDS-related applications are due by 5:00 pm EDT on October 27, 2022 and June 27, 2023, while HIV/AIDS-related applications are due January 7, 2023 and September 7, 2023.

“Discipline-specific training on sex and gender, such as what will be supported through the GENDER R25, provides pharmacy professionals with an opportunity to advance pharmacy education, research, and practice—and therefore improve human health,” Barr said. “The benefits of improved inclusion in clinical studies and enhanced integration of sex and gender in all aspects of pharmacy study and care are impressive and attainable.”

Additionally, ORWH will be offering other

 resources and programs for career development and interprofessional education

Bench to Bedside: Integrating Sex and Gender to Improve Human Health

Developed in partnership with the FDA Office of Women’s Health, the course explores sex- and gender-related differences in key disease areas. The 6 modules included provide biomedical researchers, clinicians, and students in health care professions with knowledge they can use when designing and conducting research and/or interpreting evidence for clinical practice.

Developed with funding support from the National Institute of General Medical Sciences, the course helps investigators understand and apply the NIH Policy on Sex as a Biological Variable (SABV) in research design, analyses, and reporting. The 4 modules of the course address basic, preclinical, clinical, and population health studies.

The 6-module course is designed for the biomedical research community to account for and appropriately teach the SABV policy.

Introduction: Sex- and Gender-Related Differences in Health

A self-paced introductory training aimed at researchers, clinicians, and policymakers, the downloadable slide deck and accompanying facilitator’s guide can be used by individuals or teams to initiate a dialogue about how—and why—it may be beneficial to incorporate a sex-and-gender lens into research and clinical care.

GENDER R25 will provide funding for courses and curricula to improve gender-focused education and equity in pharmacy, as well as other health care fields.

New NIH Program Funds Efforts to Improve Gender Equity in Science, Health Care Fields

Older adults have been disproportionately affected by the rising incidence of herpes zoster over the past several decades. In addition to potential postherpetic neuralgia, older adults also have a heightened risk for stroke or myocardial infarction and may require different interventions than younger individuals with herpes zoster.

Some studies have indicated a 4-fold increase in herpes zoster incidence since the 1940s, particularly impacting elderly individuals and women. This increase is happening globally and appears to be independent of demographic shifts seen with a growing elderly population and increased prevalence of immunocompromised individuals.

The lifetime risk of herpes zoster in the general population ranges from 20% to 30%, but the risk increases significantly after 50 years of age with a lifetime risk reaching 50% at 85 years of age. Current estimates show more than 1 million cases of herpes zoster in the United States each year, costing the health care system $5 billion annually. Although herpes zoster was originally not believed to occur more than once in an individual, it is now estimated to recur in approximately 6.4% of immunocompetent individuals and the recurrence rate is higher among immunocompromised individuals.

Older age is a risk factor for reactivation, as well as immunocompromised state due to conditions such as HIV infection, lymphoma, leukemia, bone marrow transplant, solid organ transplant, and immunosuppressive medications. Some data associate depression with the development of herpes zoster, in addition to potential links between weight loss and sleep disturbances.

A hallmark of herpes zoster is that following resolution of the original rash, individuals may experience additional sequelae. For older adults in particular, these may have adverse effects (AEs) on functional status, independence, and quality of life.

Although postherpetic neuralgia gradually resolves in most older adults, a subset of patients may be refractory to pain management and may experience worsening pain over time. Risk factors for the development of postherpetic neuralgia include prodromal symptoms, more severe pain and rash extent, older age, immunosuppression, diabetes, and presence of zoster ophthalmicus.

Research has also shown that adults 50 years of age and older have a heightened risk of stroke or myocardial infarction for 3 to 12 months following an episode of herpes zoster. These study findings are supported by the presence of varicella zoster virus in intracerebral and coronary arteries of these patients in postmortem studies.

Manifestations of varicella zoster virus central nervous system (CNS) vasculopathy range from transient ischemic attacks, stroke, aneurysm, subarachnoid and intracerebral hemorrhage, spinal cord infarction, cerebral venous sinus thrombosis, vision loss, giant cell temporal arteritis, or other focal neurological deficits. The mortality rate of untreated varicella zoster virus CNS vasculopathy is nearly 25%, but treatment with antiviral medications may be curative.

Treatment of herpes zoster in older adults encompasses treatment of the virus itself using antivirals and treatment of the sequelae with other agents. Antiviral therapy for acute herpes zoster fulfilling any of the following criteria: patients older than 50 years of age, moderate to severe rash or pain, those with non-truncal involvement, and those who are immunocompromised. Corticosteroids may improve the pain associated with herpes zoster and mild pain can be treated with analgesics.

Tricyclic antidepressants can also play a role in pain control associated with both acute herpes zoster and postherpetic neuralgia. Although several studies suggest that amitriptyline significantly reduces the pain of postherpetic neuralgia, nortriptyline and desipramine are preferred due to their better anticholinergic AE profile.

Topical lidocaine patches are one of the best tolerated options for pain control in postherpetic neuralgia, although patients should be advised to take care that it is applied only to the area of intact skin. Topical capsaicin is also an effective alternative for postherpetic neuralgia, although it is not recommended for acute herpes zoster pain due to the intense burning sensation.

Prevention and education efforts about herpes zoster are also essential for older adults. Vaccines may decline in efficacy over time, and pharmacists can educate older adults about this issue while encouraging them to remain up to date on vaccination.

John A and Canaday DH. Herpes zoster in the older adult. 

 December 2017. Accessed September 13, 2022. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724974/

Pharmacists can educate older adults on risk factors and prevention efforts around herpes zoster.

Older Adults With Herpes Zoster Have Unique Considerations

With intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) available for patients with chronic inflammatory demyelinating polyneuropathy (CIDP), researchers have identified a need for information to assist clinicians and patients in choosing the optimal approach.

 outlined considerations for pharmacokinetics, administration procedures, adverse events, patient variables, and cost.

CIDP is an acquired neurological condition characterized by weakness and impaired sensory function evolving over 2 months or more, loss or decrease in deep tendon reflexes, and by electrophysiological evidence of peripheral nerve demyelination. Efficient diagnosis and treatment early in the course of disease is essential to avoid irreversible disability.

IVIG is utilized both as a first-line and as a maintenance therapy option for patients with CIDP. Other first-line treatments with proven efficacy include corticosteroids and plasmapheresis. In addition, the FDA approved SCIG in 2018 for patients with CIDP, opening up new treatment options for maintenance therapy. However, researchers have identified a need for more information about the differences between IVIG and SCIG.

The efficacy of IVIG was established in 5 randomized, placebo-controlled trials conducted between 1993 and 2008. Based on these trials, clinicians have high quality evidence that IVIG is safe and effective for CIDP induction and maintenance treatment. In particular, the ICE study found that patients receiving IVIG reported significant improvements in the physical functioning, role-physical, social functioning, and mental health domains of a quality-of-life assessment.

The efficacy and safety of SCIG as maintenance therapy was established in the Polyneuropathy and Treatment with Hizentra (PATH) study of 172 IVIG-dependent patients with CIDP. Participants were randomly assigned to receive SCIG 0.2 g/kg per week, which is 40% lower than the IVIG trial, or 0.4 g/kg per week, which is 20% higher than the IVIG trial, or placebo for 24 weeks.

The primary outcome was the proportion of patients who relapsed or withdrew from the study for any reason during the 24-week treatment period. Those who relapsed during SC therapy were rescued with IVIG and discontinued.

In the placebo arm, 63% of patients relapsed or withdrew from the study, compared to 39% in the low-dose group and 33% in the high-dose group. When only relapse was considered, 56% of patients treated with placebo relapsed in the 24-week period, compared to 33% of low-dose and 19% of high-dose treated patients.

Among patients receiving SCIG therapy, 53% stated a preference for SCIG compared to 39% of patients in the placebo group. Reasons for this preference included increased independence and fewer adverse effects (AEs). Eighteen percent of patients receiving SCIG said that they preferred their previous IVIG treatment.

Considering pharmacokinetics, AE profiles, site of care, patient preference variables, and economics is also important.

After an IVIG infusion, the concentration of immunoglobulin G (IgG) peaks within minutes and falls by approximately half over the next 2 to 3 days. Following this rapid equilibration, IgG is catabolized with first-order kinetics and a half-life of 21 to 30 days.

Importantly, the optimal pharmacokinetic parameters for the treatment of CIDP are unknown. Although pharmacokinetic parameters are important considerations for optimizing the efficacy of immunoglobulin, the authors said there are still many questions.

The key principle in pharmacokinetics is that the dose and treatment intervals required to achieve and maintain any given clinical response vary greatly between individuals. Identifying those differences may help clinicians take advantage of differences between SCIG and IVIG pharmacokinetics.

The most common systemic IVIG AEs are headaches and nausea. Many IVIG AEs can be managed with adequate hydration and medications, such as antihistamines, acetaminophen, and corticosteroids, as well as slowing the infusion rate or switching to a different IVIG preparation. Systemic AEs of SCIG are similar, although the frequency and severity with SCIG infusions are generally fewer than with IVIG.

Because SCIG requires no IV access, patients with difficult IV access may be good candidates for SCIG. The most common AE reported that is unique to SCIG is local infusion site reactions, such as redness, itching, or swelling.

Currently, patients with CIDP can receive immunoglobulin therapy in a hospital clinic, physician’s office, a free-standing infusion clinic, or at home. Although IVIG is overseen by a nurse, most SCIG maintenance regimens can be administered by the patient or caregiver without the need for other medical support staff. Patients can travel with their SCIG, removing the need to be near an infusion center or other facility at a fixed interval.

Surveys have also found that patients enjoy the convenience, autonomy, and at-home administration associated with SCIG. However, handling needles and medical equipment weekly without the support of a trained health care professional may be limiting for some patients, particularly those with upper limb disability.

Finally, the authors noted that the economics of IVIG versus SCIG for CDIP are not well understood. A hypothetical cost analysis showed that the low-dose SCIG regimen resulted in a $900 cost savings compared to the IVIG regimen ($8248 versus $9131 over 3 weeks). However, when the high-dose SCIG regimen is required, the costs to the payer would nearly double. These findings are also consistent with findings from European analyses, demonstrating that the cost of the immunoglobulin formulation is often the primary driver of the overall cost of CIDP treatment, according to the study.

With all of these considerations in mind, the authors emphasized the need to consider patients’ individual needs and preferences. The decision to use either SCIG or IVIG should be tailored to patient disease characteristics, treatment goals, and lifestyle. Although there is no “best” way to determine which route of administration is best, health care providers are optimally positioned to educate patients and help them make the best decision.

Allen JA, Gelinas DF, Freimer M, Runken MC, and Wolfe GI. Immunoglobulin administration for the treatment of CIDP: IVIG or SCIG? 

; November 9, 2019. Accessed September 13, 2022. 

https://www.jns-journal.com/article/S0022-510X(19)30429-0/fulltext

Although there is no “best” way to determine which route of administration is best, health care providers are optimally positioned to educate patients and help them make the best decision.

Options for Immunoglobulin Administration Allow for Personalized Treatment of Chronic Inflammatory Demyelinating Polyneuropathy

Despite the fact that pharmacy technicians perform the majority of aseptic compounding practices, the loss of aseptic technique and knowledge over time can result in unsafe, non-sterile compounding, according to a study published in the 

. Subsequently, the study authors are advocating for continuing education efforts to address pharmacy technician sterile compounders.

Several prior studies have found that poor technique or failure to follow up-to-date standards and protocols could lead to injury or even death of patients. Between 2001 and 2013, researchers identified 19 outbreaks of infections that were linked to compounded sterile products. At least 1000 patients were affected in these outbreaks, with some cases resulting in death.

The investigators also noted that Texas is currently the only state requiring sterile compounding training or continuing education hours for technicians making compounded sterile products in the state. Furthermore, uniform prerequisites for employing pharmacy technicians are currently nonexistent, according to the study.

In the study, the authors looked at the links between sterile compounding knowledge and years in the field, while controlling for formal training in sterile compounding techniques. They distributed an assessment tool to members of pharmacy organizations in the southeastern United States who are sterile compounding pharmacy technicians and conducted a multiple regression to predict sterile compounding knowledge from the number of years in the field and prior years of training.

Seventy assessments were attempted and 2 were excluded due to failure of completion or submission. The majority of participants were female and the most common education level among participants was a program diploma. The number of training hours ranged from 0 to 240 hours, the number of years in the field ranged from 1 to 28 years, and assessment scores ranged from 18 to 30 points.

According to the study, participants with bachelor’s degrees averaged higher scores, followed closely by participants with associate degrees. Those with program diplomas and high school graduates scored lower.

The investigators also found that length of experience is a statistically significant predictor of knowledge retention. For every additional year of work experience, they found that the knowledge test score decreased by 0.18 points. However, the number of formal training hours was found to be nonsignificant to the prediction.

One potential explanation could be knowledge loss due to the modeling of actions seen in other pharmacy staff. The researchers explained that employees replicate behaviors seen in their surroundings and newer pharmacy technicians may be particularly prone to this. Over time, failure to be corrected when incorrectly performing a task results in loss of skills and knowledge.

“Failure to be corrected about unsatisfactory processes encourages the continuation of such practices and creates a sense of expected acceptance of all compounded products,” the authors explained.

In order to avoid this loss of knowledge, the authors said mandatory continued education at predetermined intervals may be necessary. Implementing knowledge retention strategies in the workplace may also improve knowledge loss and providing incentives for staying current with sterile compounding practices could be effective.

This could include access to continuing education credits or monetary bonuses. In addition, the researchers said appointing a person to oversee knowledge retention activities may be necessary, including identifying employees exhibiting a decline in work performance.

“Even a slight loss of competency is a significant concern in sterile medication compounding because every aspect of the sterile compounding process is critical to patient safety,” the study authors wrote. “The findings of this study should be of interest to all pharmacy staff.”

David J., and Ayars C. Retention of Sterile Compounding Knowledge Among Pharmacy Technicians. 

 2021 Oct; 37(5): 219-224. July 20, 2021. Accessed September 13, 2022. doi:10.1177/87551225211032395

Research indicates that poor technique or failure to follow up-to-date standards and protocols could lead to injury or even death of patients who need compounded medications.

Continuing Education for Pharmacy Technicians Essential for Safe, Sterile Compounding

New data from the phase 1b/2 EV-103 clinical trial cohort K support ongoing research into the use of enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab, and enfortumab vedotin-ejfv alone in patients with unresectable locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-based chemotherapy.

Results demonstrated a 64.5% confirmed objective response rate (ORR) in patients treated with the investigational combination. The data were highlighted in a late-breaking presentation at the European Society for Medical Oncology Congress 2022.

“Nearly 65% of patients who were treated with enfortumab vedotin and pembrolizumab responded to this combination, with almost 11% showing no detectable cancer following treatment,” said Margorie Green, senior vice president and head of late-stage development at Seagen, in a press release. “These study results represent an encouraging finding for people with advanced urothelial cancer who are not eligible for cisplatin treatment.”

The confirmed ORR was the primary endpoint of cohort K, with 10.5% of patients experiencing a complete response and 53.9% of patients experiencing a partial response. The median duration of response (DOR) was not reached.

All-grade treatment-related adverse events (TRAEs) of special interest for enfortumab vedotin-ejfv in combination with pembrolizumab were skin reactions (67.1%), peripheral neuropathy (60.5%), ocular disorders (26.3%), hyperglycemia (14.5%), and infusion-related reactions (3.9%). Pembrolizumab AEs of special interest were consistent with previously observed safety data from monotherapy with the exception of severe skin reactions.

Cohort K of the trial also included a monotherapy arm in which 73 patients were treated with enfortumab vedotin-ejfv alone, although the study was not designed to support a formal comparison between the 2 arms. Results from this cohort showed a 45.2% confirmed ORR, with 4.1% of patients experiencing a complete response and 41.1% of patients experiencing a partial response. The median DOR was 13.2 months.

All-grade TRAEs of special interest for enfortumab vedotin-ejfv were peripheral neuropathy (54.8%), skin reactions (45.2%), ocular disorders (28.8%), hyperglycemia (11%), and infusion-related reactions (5.5%).

“We’re pleased that this combination provided a meaningful benefit to this group of advanced bladder cancer patients in this study, and we will continue to investigate enfortumab vedotin plus pembrolizumab through our collaboration,” said Eliav Barr, MD, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, in the press release.

Additional secondary endpoints in Cohort K included progression-free survival (PFS) and overall survival (OS). Among patients treated with both enfortumab vedotin-ejfv and pembrolizumab, median PFS was not reached, and median OS was 22.3 months. Among those treated with enfortumab vedotin-ejfv alone, median PFS was 8 months and median OS was 21.7 months.

TRAEs of any grade that occurred in more than 20% of patients treated with enfortumab vedotin-ejfv alone or in combination with pembrolizumab were fatigue, peripheral sensory neuropathy, alopecia, rash maculo-papular, pruritus, dysgeusia, decreased weight, diarrhea, decreased appetite, nausea, and dry eye.

In February 2020, the FDA granted Breakthrough Therapy Designation to enfortumab vedotin-ejfv in combination with pembrolizumab for patients with unresectable la/mUC who are ineligible to receive cisplatin-based chemotherapy in the first-line setting. The designation is based on results from the dose-escalation cohort and expansion cohort A in the phase 1b/2 EV-103 trial.

“We’re encouraged by these positive findings from the combination of enfortumab vedotin and pembrolizumab in people with advanced urothelial cancer who historically have had limited treatment options in the first-line setting, and we intend to discuss these results with regulatory authorities,” said Ahsan Arozullah, MD, MPH, senior vice president and head of development therapeutic areas at Astellas, in the press release.

Seagen, Astellas, and Merck Announce Results of Clinical Trial Investigating Padcev (enfortumab vedotin-ejfv) with Keytruda (pembrolizumab) and Padcev as Monotherapy in First-Line Advanced Urothelial Cancer. News release. Merck; September 12, 2022. Accessed September 13, 2022. 

https://www.merck.com/news/seagen-astellas-and-merck-announce-results-of-clinical-trial-investigating-padcev-enfortumab-vedotin-ejfv-with-keytruda-pembrolizumab-and-padcev-as-monotherapy-in-first-line-advanced/

Results demonstrated a 64.5% confirmed objective response rate in patients treated with the investigational combination.